In the field of synthetic organic chemistry there is great interest in the synthesis of fluoro analogs of known biologically active compounds, such as insecticides, pheromones or pharmaceuticals. As described by R. Filler, Chemtech 1974, 752, fluorine as a substituent most closely resembles hydrogen with respect to steric requirements at enzyme receptor sites. However, because of its high electro-negativity, fluorine substitution alters the electronic behavior of the compound. Since the carbon-fluorine bond energy is very high, the fluorine substituent imparts increased oxidative and thermal stability. Fluorine substitution also leads to increased lipid solubility in membranes, thus enhancing the rates of absorption and transport of the compound. Thus fluoro compounds often show similar types of biological activity to their hydrogen analogs but modified by differences in absorption, transport and metabolic rates. As indicated in the above reference, in the pharmaceutical field fluorine substitution has provided compounds of great importance in cancer treatment as well as anesthetics, tranquilizers, adrenocortical and anti-inflammatory drugs, progestational agents and drugs for androgenic hormone therapy.
In the synthetic pathways to fluoro analogs of known biologically active compounds (Z)-2-fluoro-2-alkenoate esters and their derivatives provide valuable intermediates. Syntheses of these esters are described in the following chemical journal articles: Machleidt, H.; Wessendorf, R. Liebigs Ann. 1964, 674, 1. Tarrant, P.; Johncock, P.; Savory, J. J. Org. Chem. 1963, 28, 839; Bergmann, E. D.; Shahak, I.; Sali, E.; Aizenshtat, Z. J. Chem. Soc. C 1968, 1232; Dedek, V.; Kovak, M. Coll. Czechoslov. Chem. Commun. 1979, 44, 2660; Kitazume, T.; Ishikawa, N. Chemistry Lett. 1981, 1259; Kobayashi, Y.; Morikawa, T.; Yoshizawa, A.; Taguchi, T. Tetrahedron Lett. 1981, 22, 5297; Blanco, L.; Rousseau, G. Bull. Soc. Chim. Fr. 1985, 3, 455; and Nakayama, Y.; Kitazume, T.; Ishikawa, N. J. Fluorine Chem. 1985, 29, 445. However, existing methods for the preparation of 2-fluoro--alkenoate esters have the disadvantages of complexity and high cost. Moreover, most of these methods yield mixtures of the two geometric stereoisomers which are possible about the double bond of the alkene chain. For biological purposes it is desirable to produce a single preferred stereoisomer.